%0 Journal Article
%T Archaeal Ubiquitin-Like Proteins: Functional Versatility and Putative Ancestral Involvement in tRNA Modification Revealed by Comparative Genomic Analysis
%A Kira S. Makarova
%A Eugene V. Koonin
%J Archaea
%D 2010
%I Hindawi Publishing Corporation
%R 10.1155/2010/710303
%X The recent discovery of protein modification by SAMPs, ubiquitin-like (Ubl) proteins from the archaeon Haloferax volcanii, prompted a comprehensive comparative-genomic analysis of archaeal Ubl protein genes and the genes for enzymes thought to be functionally associated with Ubl proteins. This analysis showed that most archaea encode members of two major groups of Ubl proteins with the -grasp fold, the ThiS and MoaD families, and indicated that the ThiS family genes are rarely linked to genes for thiamine or Mo/W cofactor metabolism enzymes but instead are most often associated with genes for enzymes of tRNA modification. Therefore it is hypothesized that the ancestral function of the archaeal Ubl proteins is sulfur insertion into modified nucleotides in tRNAs, an activity analogous to that of the URM1 protein in eukaryotes. Together with additional, previously described genomic associations, these findings indicate that systems for protein quality control operating at different levels, including tRNA modification that controls translation fidelity, protein ubiquitination that regulates protein degradation, and, possibly, mRNA degradation by the exosome, are functionally and evolutionarily linked. 1. Introduction Ubiquitination (ubiquitylation) of proteins is an ancestral, pivotal process in eukaryotes that governs protein trafficking and turnover, signaling, heterochromatin remodeling, and other processes [1¨C3]. All eukaryotes possess an elaborate system that includes a variety of small proteins of the ubiquitin (Ub) family, E1 Ub-activating, E2 Ub-conjugating, and E3 Ub-ligase enzymes, as well as a broad diversity of deubiquitinating enzymes (DUBs) [1, 2, 4]. Ubiquitin conjugation through the formation of isopeptide bonds by the e-amino groups of two conserved lysines of the Ub molecule (K48 and K63) determines the fate of most proteins in eukaryotic cells, in terms of both topogenesis and degradation. The functioning of Ub-centered signaling systems is regulated through the activities of numerous, specific Ub-binding domains and proteins. Ubiquitin is one of the most highly conserved eukaryotic proteins, and the evolution of the Ub system is fairly well studied [1, 5¨C8]. In particular, it has been shown that Ub homologs in bacteria and most likely in archaea are involved in thiamine and molybdenum (Mo)/tungsten (W) cofactor biosynthesis along with functionally linked homologs of E1 enzymes; in addition, E2 family proteins and homologs of metal-dependent DUBs of the Jab1/MPN family have been detected in several bacteria in association with Ub-like
%U http://www.hindawi.com/journals/archaea/2010/710303/